Mass Spectrometer

ABSTRACT

A mass spectrometer is disclosed comprising a first ion trap or ion guide, a single ion mobility spectrometer or separator stage and a second ion trap or ion guide arranged downstream of the ion mobility spectrometer or separator. A mode of operation includes passing ions from said first ion trap or ion guide to said device and onwards to said second ion trap or ion guide and then passing at least some of said ions or at least some fragment, daughter, product or adduct ions derived from said ions from said second ion trap or ion guide onwards to said first ion trap or ion guide

CROSS-REFERENCE TO RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.12/092,601 filed on Aug. 20, 2008 which represents a National Stage ofInternational Application No. PCT/GB2006/004202 filed on Nov. 10, 2006and claims the benefit of U.S. Provisional Patent Application Ser. No.60/737,150 filed on Nov. 16, 2005 and United Kingdom Application No.0522933.1 filed on Nov. 10, 2005. The entire contents of theseapplications are incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention relates to a mass spectrometer and a method ofmass spectrometry.

Mass spectrometry is an established technique for identifying andquantifying molecules, including molecules of biological interest. It isa primary technique for identifying proteins due to its unparalleledspeed, sensitivity and specificity. Strategies for the analysis ofproteins may involve either analysis of the intact protein or morecommonly digestion of the protein using a specific protease that cleavesat predictable residues along the peptide backbone. This providessmaller stretches of peptide sequence that are more amenable to analysisvia mass spectrometry.

It is known to perform experiments which involve the separation of acomplex digest mixture by liquid chromatography which is directlyinterfaced to a tandem mass spectrometer using Electrospray Ionisation(ESI). MS and MS/MS spectra may be collected throughout thechromatographic separation and this information may be used to searchdatabases directly for matching sequences leading to identification ofthe parent protein.

The known approach can be used to identify proteins that are present atlow endogenous concentrations. However, such digest mixtures may containmany hundreds if not thousands of components many of which will co-elutefrom the chromatography column. Methods designed for analysis of digestmixtures aim to identify as many of the peaks as possible within thecomplex mixture. However, as sample complexity increases it becomesincreasingly difficult to select each individual precursor or parent ionfor subsequent fragmentation.

One method of increasing the peak capacity is to fragment a large numberof parent or precursor ions simultaneously and then to record theirproduct or fragment ions. Product or fragment ions may be associatedwith parent or precursor ions according to the closeness of alignment oftheir LC elution times. Eventually, however, as the sample complexityincreases this method may also fail.

Another approach to the problem of highly complex mixtures is to improvethe separation capability. Addition of a further orthogonal separationstage can be particularly effective, especially if the time requirementsfor each separation process and for the mass spectrometer do notoverlap.

One known method which may be used to separate ions prior to analysis bymass spectrometry is that of ion mobility spectrometry or gas phaseelectrophoresis. One form of an ion mobility spectrometer or separatorcomprises a drift tube or cell wherein an axial electric field ismaintained in the presence of a buffer gas. Higher mobility ions passmore quickly along the length of the ion mobility spectrometer orseparator than lower mobility ions. As a result ions are separatedaccording to their ion mobility.

A known ion mobility spectrometer or separator may operate at or aroundatmospheric pressure or under a partial vacuum at a pressure down to aslow as about 0.01 mbar. The known ion mobility spectrometer or separatoroperating under a partial vacuum comprises a plurality of electrodeshaving apertures. A DC voltage gradient is maintained along the lengthof the ion mobility spectrometer or separator and the electrodes areconnected to an AC or RF voltage supply. This form of ion mobilityspectrometer or separator is advantageous in that the AC or RF voltagewhich is applied to the electrodes results in radial confinement of theions passing through the ion mobility spectrometer or separator. Radialconfinement of the ions results in higher ion transmission compared withan ion mobility spectrometer or separator which does not confine ionsradially.

An ion mobility spectrometer or separator is known wherein ions areconfined radially by an inhomogeneous RF field in an ion guide and ionsare propelled forward by a potential hill or barrier that isprogressively applied along the axis of the ion guide in the presence ofa buffer gas. Appropriate selection of the amplitude and velocity of thepotential hill or barrier which is translated along the length of theion guide and the type and pressure of gas allows ions to slipselectively over the potential hill or barrier according to their ionmobility. This in turn allows ions having different ion mobilities to betransported at different velocities along the ion guide and thereby tobecome temporally separated.

The additional separation gained by the use of ion mobility separation(IMS) or gas phase electrophoresis increases the peak capacity of a massspectrometer. This benefit is gained irrespective of whether or notother separation techniques such as Liquid Chromatography (LC) are alsoused. Furthermore, the benefit gained by the use of ion mobilityseparation is equally relevant to tandem mass spectrometers (MS/MS) inwhich parent ions may be mass analysed and then selected parent ions maybe induced to fragment by Collision Induced Decomposition and whereinthe resulting fragment or daughter ions are then mass analysed.

It is desired to provide a mass spectrometer having an improved abilityto separate ions according to their ion mobility.

SUMMARY OF THE INVENTION

According to an aspect of the present invention there is provided a massspectrometer comprising:

a first ion trap or ion guide comprising a plurality of electrodes;

a device for separating ions according to their ion mobility or rate ofchange of ion mobility with electric field strength, the device beingarranged downstream of the first ion trap or ion guide; and

a second ion trap or ion guide comprising a plurality of electrodesarranged downstream of the device, wherein the second ion trap or ionguide is arranged and adapted in a mode of operation to pass or transmitions from the second ion trap or ion guide to the device.

According to the preferred embodiment the first ion trap or ion guide ispreferably arranged and adapted in a mode of operation to receive ionswhich emerge from the device. The first ion trap or ion guide ispreferably arranged and adapted in a mode of operation to receive ionswhich emerge from the device and to pass or transmit at least some ofthe ions, or at least some fragment, daughter, product or adduct ionsderived from the ions, from the first ion trap or ion guide to thedevice.

The first ion trap or ion guide may comprise a multipole rod set or asegmented multipole rod set ion trap or ion guide comprising aquadrupole rod set, a hexapole rod set, an octapole rod set or a rod setcomprising more than eight rods. Alternatively, the first ion trap orion guide may comprise an ion tunnel or ion funnel ion trap or ion guidecomprising a plurality of electrodes or at least 2, 5, 10, 20, 30, 40,50, 60, 70, 80, 90 or 100 electrodes having apertures through which ionsare transmitted in use, wherein at least 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%of the electrodes have apertures which are of substantially the samesize or area or which have apertures which become progressively largerand/or smaller in size or in area. According to another embodiment thefirst ion trap or ion guide may comprise a stack or array of planar,plate or mesh electrodes, wherein the stack or array of planar, plate ormesh electrodes comprises a plurality or at least 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 planar, plate or meshelectrodes and wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of theplanar, plate or mesh electrodes are arranged generally in the plane inwhich ions travel in use. According to another embodiment the first iontrap or ion guide may comprise an ion trap or ion guide comprising aplurality of groups of electrodes arranged axially along the length ofthe ion trap or ion guide, wherein each group of electrodes comprises:(a) a first and a second electrode and means for applying a DC voltageor potential to the first and second electrodes in order to confine ionsin a first radial direction within the ion guide; and (b) a third and afourth electrode and means for applying an AC or RF voltage to the thirdand fourth electrodes in order to confine ions in a second radialdirection within the ion guide. The second radial direction ispreferably orthogonal to the first radial direction.

According to the preferred embodiment the first ion trap or ion guidecomprises an ion tunnel or ion funnel ion trap or ion guide wherein atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes have internaldiameters or dimensions selected from the group consisting of: (i) ≦1.0mm; (ii) ≦2.0 mm; (iii) ≦3.0 mm; (iv) ≦4.0 mm; (v) ≦5.0 mm; (vi) ≦6.0mm; (vii) ≦7.0 mm; (viii) ≦8.0 mm; (ix) ≦9.0 mm; (x) ≦10.0 mm; and(xi) >10.0 mm.

The first ion trap or ion guide preferably further comprises first AC orRF voltage means arranged and adapted to apply an AC or RF voltage to atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the plurality of electrodes ofthe first ion trap or ion guide in order to confine ions radially withinthe first ion trap or ion guide. The first AC or RF voltage means ispreferably arranged and adapted to apply an AC or RF voltage having anamplitude selected from the group consisting of: (i) <50 V peak to peak;(ii) 50-100 V peak to peak; (iii) 100-150 V peak to peak; (iv) 150-200 Vpeak to peak; (v) 200-250 V peak to peak; (vi) 250-300 V peak to peak;(vii) 300-350 V peak to peak; (viii) 350-400 V peak to peak; (ix)400-450 V peak to peak; (x) 450-500 V peak to peak; and (xi) >500 V peakto peak. The first AC or RF voltage means is preferably arranged andadapted to apply an AC or RF voltage having a frequency selected fromthe group consisting of: (i) <100 kHz; (ii) 100-200 kHz; (iii) 200-300kHz; (iv) 300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5MHz; (viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5MHz; (xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz; (xv)5.0-5.5 MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz;(xix) 7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5-9.0MHz; (xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and (xxv) >10.0 MHz.

The first ion trap or ion guide is preferably arranged and adapted toreceive a beam or group of ions and to convert or partition the beam orgroup of ions such that a plurality or at least 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 separate packets of ionsare confined and/or isolated in the first ion trap or ion guide at anyparticular time. Each packet of ions is preferably separately confinedand/or isolated in a separate real axial potential well formed withinthe first ion trap or ion guide.

The mass spectrometer preferably further comprises means arranged andadapted to urge at least some ions upstream and/or downstream through oralong at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial length ofthe first ion trap or ion guide in a mode of operation.

According to the preferred embodiment first transient DC voltage meansare provided which are arranged and adapted to apply one or moretransient DC voltages or potentials or one or more transient DC voltageor potential waveforms to the electrodes forming the first ion trap orion guide in order to urge at least some ions upstream and/or downstreamalong at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial length ofthe first ion trap or ion guide.

According to a less preferred embodiment AC or RF voltage means may beprovided and may be arranged and adapted to apply two or morephase-shifted AC or RF voltages to electrodes forming the first ion trapor ion guide in order to urge at least some ions upstream and/ordownstream along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the axiallength of the first ion trap or ion guide.

The mass spectrometer preferably comprises means arranged and adapted ina mode of operation to maintain at least a portion of the first ion trapor ion guide at a pressure selected from the group consisting of:(i) >0.0001 mbar; (ii) >0.001 mbar; (iii) >0.01 mbar; (iv) >0.1 mbar;(v) >1 mbar; (vi) >10 mbar; (vii) >1 mbar; (viii) 0.0001-100 mbar; and(ix) 0.001-10 mbar.

According to an embodiment first acceleration means are preferablyprovided which are arranged and adapted to accelerate ions into thefirst ion trap or ion guide wherein in a mode of operation at least 5%,10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%, 95% or 100% of the ions are caused to fragment or reactupon entering the first ion trap or ion guide. The first accelerationmeans preferably accelerates ions from the ion mobility spectrometer orseparator into the first ion trap or ion guide.

A control system is preferably arranged and adapted to switch orrepeatedly switch the potential difference through which ions pass priorto entering the first ion trap or ion guide between a relatively highfragmentation or reaction mode of operation wherein ions aresubstantially fragmented or reacted upon entering the first ion trap orion guide and a relatively low fragmentation or reaction mode ofoperation wherein substantially fewer ions are fragmented or reacted orwherein substantially no ions are fragmented or reacted upon enteringthe first ion trap or ion guide. In the relatively high fragmentation orreaction mode of operation ions entering the first ion trap or ion guideare preferably accelerated through a potential difference selected fromthe group consisting of: (i) ≧10 V; (ii) ≧20 V; (iii) ≧30 V; (iv) ≧40 V;(v) ≧50 V; (vi) ≧60 V; (vii) ≧70 V; (viii) ≧80 V; (ix) ≧90 V; (x) ≧100V; (xi) ≧110 V; (xii) ≧120 V; (xiii) ≧130 V; (xiv) ≧140 V; (xv) ≧150 V;(xvi) ≧160 V; (xvii) ≧170 V; (xviii) ≧180 V; (xix) ≧190 V; and (xx) ≧200V. In the relatively low fragmentation or reaction mode of operationions entering the first ion trap or ion guide are preferably acceleratedthrough a potential difference selected from the group consisting of:(i) ≦20 V; (ii) ≦15 V; (iii) ≦10 V; (iv) ≦5V; and (v) ≦1V.

The device which is preferably arranged downstream of the first ion trapor ion guide preferably comprises an ion mobility spectrometer orseparator which is preferably arranged to separate ions according totheir ion mobility. The device preferably comprises a gas phaseelectrophoresis device.

The ion mobility spectrometer or separator is preferably arranged totemporally separate ions according to their ion mobility which emergefrom or which have been transmitted or received from the first ion trapor ion guide and/or the second ion trap or guide.

The ion mobility spectrometer or separator may comprise either: (i) adrift tube comprising one or more electrodes and means for maintainingan axial DC voltage gradient or a substantially constant or linear axialDC voltage gradient along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%,40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% ofthe axial length of the drift tube; (ii) a multipole rod set or asegmented multipole rod set comprising a quadrupole rod set, a hexapolerod set, an octapole rod set or a rod set comprising more than eightrods; (iii) an ion tunnel or ion funnel comprising a plurality ofelectrodes or at least 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100electrodes having apertures through which ions are transmitted in use,wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes haveapertures which are of substantially the same size or area or which haveapertures which become progressively larger and/or smaller in size or inarea; (iv) a stack or array of planar, plate or mesh electrodes, whereinthe stack or array of planar, plate or mesh electrodes comprises aplurality or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19 or 20 planar, plate or mesh electrodes wherein at least5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%,75%, 80%, 85%, 90%, 95% or 100% of the planar, plate or mesh electrodesare arranged generally in the plane in which ions travel in use; or (v)a plurality of groups of electrodes arranged axially along the length ofthe ion trap or ion guide, wherein each group of electrodes comprises:(a) a first and a second electrode and means for applying a DC voltageor potential to the first and second electrodes in order to confine ionsin a first radial direction within the device; and (b) a third and afourth electrode and means for applying an AC or RF voltage to the thirdand fourth electrodes in order to confine ions in a second radialdirection (which is preferably orthogonal to the first radial direction)within the device.

According to the preferred embodiment the ion mobility spectrometer orseparator preferably comprises an ion tunnel or ion funnel wherein atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the electrodes have internaldiameters or dimensions selected from the group consisting of: (i) ≦1.0mm; (ii) ≦2.0 mm; (iii) ≦3.0 mm; (iv) ≦4.0 mm; (v) ≦5.0 mm; (vi) ≦6.0mm; (vii) ≦7.0 mm; (viii) ≦8.0 mm; (ix) ≦9.0 mm; (x) ≦10.0 mm; and(xi) >10.0 mm.

The ion mobility spectrometer or separator preferably further comprisesa second AC or RF voltage means arranged and adapted to apply an AC orRF voltage to at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the plurality ofelectrodes of the ion mobility spectrometer or separator in order toconfine ions radially within the ion mobility spectrometer or separator.The second AC or RF voltage means is preferably arranged and adapted toapply an AC or RF voltage having an amplitude selected from the groupconsisting of: (i) <50 V peak to peak; (ii) 50-100 V peak to peak; (iii)100-150 V peak to peak; (iv) 150-200 V peak to peak; (v) 200-250 V peakto peak; (vi) 250-300 V peak to peak; (vii) 300-350 V peak to peak;(viii) 350-400 V peak to peak; (ix) 400-450 V peak to peak; (x) 450-500V peak to peak; and (xi) >500 V peak to peak. The second AC or RFvoltage means is preferably arranged and adapted to apply an AC or RFvoltage having a frequency selected from the group consisting of: (i)<100 kHz; (ii) 100-200 kHz; (iii) 200-300 kHz; (iv) 300-400 kHz; (v)400-500 kHz; (vi) 0.5-1.0 MHz; (vii) 1.0-1.5 MHz; (viii) 1.5-2.0 MHz;(ix) 2.0-2.5 MHz; (x) 2.5-3.0 MHz; (xi) 3.0-3.5 MHz; (xii) 3.5-4.0 MHz;(xiii) 4.0-4.5 MHz; (xiv) 4.5-5.0 MHz; (xv) 5.0-5.5 MHz; (xvi) 5.5-6.0MHz; (xvii) 6.0-6.5 MHz; (xviii) 6.5-7.0 MHz; (xix) 7.0-7.5 MHz; (xx)7.5-8.0 MHz; (xxi) 8.0-8.5 MHz; (xxii) 8.5-9.0 MHz; (xxiii) 9.0-9.5 MHz;(xxiv) 9.5-10.0 MHz; and (xxv) >10.0 MHz.

According to the preferred embodiment the ion mobility spectrometer orseparator preferably comprises second transient DC voltage meansarranged and adapted to apply one or more transient DC voltages orpotentials or one or more transient DC voltage or potential waveforms toelectrodes forming the ion mobility spectrometer or separator in orderto urge at least some ions upstream and/or downstream along at least 5%,10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%, 95% or 100% of the axial length of the ion mobilityspectrometer or separator.

According to a less preferred embodiment the ion mobility spectrometeror separator may comprise AC or RF voltage means arranged and adapted toapply two or more phase-shifted AC or RF voltages to electrodes formingthe ion mobility spectrometer or separator in order to urge at leastsome ions upstream and/or downstream along at least 5%, 10%, 15%, 20%,25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%,95% or 100% of the axial length of the ion mobility spectrometer orseparator.

The mass spectrometer preferably comprises means arranged and adapted ina mode of operation to maintain at least a portion or substantially thewhole of the ion mobility spectrometer or separator at a pressureselected from the group consisting of: (i) >0.001 mbar; (ii) >0.01 mbar;(iii) >0.1 mbar; (iv) >1 mbar; (v) >10 mbar; (vi) >100 mbar; (vii)0.001-100 mbar; (viii) 0.01-10 mbar; and (ix) 0.1-1 mbar.

According to a less preferred embodiment the device arranged downstreamof the first ion trap or ion guide may comprise a Field Asymmetric IonMobility Spectrometer (“FAIMS”) device which is arranged to separateions according to their rate of change of ion mobility with electricfield strength. The Field Asymmetric Ion Mobility Spectrometer devicemay comprise at least a first electrode and a second electrode. Ions maybe arranged to be received, in use, between the first and secondelectrodes. According to an embodiment the FAIMS device may furthercomprise means for applying: (i) an asymmetric periodic voltage waveformto the first and/or second electrodes, wherein the asymmetric periodicvoltage waveform has a peak positive voltage and a peak negativevoltage; and (ii) a DC compensation voltage to the first and/or secondelectrodes, wherein the DC compensation voltage preferably acts tocounterbalance or counteract a force which would otherwise cause desiredions to drift towards the first and/or second electrodes.

According to an embodiment the second ion trap or ion guide may compriseeither: (i) a multipole rod set or a segmented multipole rod setcomprising a quadrupole rod set, a hexapole rod set, an octapole rod setor a rod set comprising more than eight rods; (ii) an ion tunnel or ionfunnel comprises a plurality of electrodes or at least 2, 5, 10, 20, 30,40, 50, 60, 70, 80, 90 or 100 electrodes having apertures through whichions are transmitted in use, wherein at least 5%, 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or100% of the electrodes have apertures which are of substantially thesame size or area or which have apertures which become progressivelylarger and/or smaller in size or in area; (iii) a stack or array ofplanar, plate or mesh electrodes, wherein the stack or array of planar,plate or mesh electrodes comprises a plurality or at least 2, 3, 4, 5,6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 planar, plateor mesh electrodes arranged generally in the plane in which ions travelin use, wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%,50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the planar,plate or mesh electrodes are arranged generally in the plane in whichions travel in use; or (iv) an ion trap or ion guide comprising aplurality of groups of electrodes arranged axially along the length ofthe ion trap or ion guide, wherein each group of electrodes comprises:(a) a first and a second electrode and means for applying a DC voltageor potential to the first and second electrodes in order to confine ionsin a first radial direction within the ion guide; and (b) a third and afourth electrode and means for applying an AC or RF voltage to the thirdand fourth electrodes in order to confine ions in a second radialdirection (which is preferably orthogonal to the first radial direction)within the ion guide.

According to an embodiment the second ion trap or ion guide preferablycomprises an ion tunnel or ion funnel wherein at least 5%, 10%, 15%,20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%,90%, 95% or 100% of the electrodes have internal diameters or dimensionsselected from the group consisting of: (i) ≦1.0 mm; (ii) ≦2.0 mm; (iii)≦3.0 mm; (iv) ≦4.0 mm; (v) ≦5.0 mm; (vi) ≦6.0 mm; (vii) ≦7.0 mm; (viii)≦8.0 mm; (ix) ≦9.0 mm; (x) ≦10.0 mm; and (xi) >10.0 mm.

The second ion trap or ion guide may further comprise third AC or RFvoltage means arranged and adapted to apply an AC or RF voltage to atleast 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%,70%, 75%, 80%, 85%, 90%, 95% or 100% of the plurality of electrodes ofthe second ion trap or ion guide in order to confine ions radiallywithin the second ion trap or ion guide. The third AC or RF voltagemeans is preferably arranged and adapted to apply an AC or RF voltagehaving an amplitude selected from the group consisting of: (i) <50 Vpeak to peak; (ii) 50-100 V peak to peak; (iii) 100-150 V peak to peak;(iv) 150-200 V peak to peak; (v) 200-250 V peak to peak; (vi) 250-300 Vpeak to peak; (vii) 300-350 V peak to peak; (viii) 350-400 V peak topeak; (ix) 400-450 V peak to peak; (x) 450-500 V peak to peak; and(xi) >500 V peak to peak. The third AC or RF voltage means is preferablyarranged and adapted to apply an AC or RF voltage having a frequencyselected from the group consisting of: (i) <100 kHz; (ii) 100-200 kHz;(iii) 200-300 kHz; (iv) 300-400 kHz; (v) 400-500 kHz; (vi) 0.5-1.0 MHz;(vii) 1.0-1.5 MHz; (viii) 1.5-2.0 MHz; (ix) 2.0-2.5 MHz; (x) 2.5-3.0MHz; (xi) 3.0-3.5 MHz; (xii) 3.5-4.0 MHz; (xiii) 4.0-4.5 MHz; (xiv)4.5-5.0 MHz; (xv) 5.0-5.5 MHz; (xvi) 5.5-6.0 MHz; (xvii) 6.0-6.5 MHz;(xviii) 6.5-7.0 MHz; (xix) 7.0-7.5 MHz; (xx) 7.5-8.0 MHz; (xxi) 8.0-8.5MHz; (xxii) 8.5-9.0 MHz; (xxiii) 9.0-9.5 MHz; (xxiv) 9.5-10.0 MHz; and(xxv) >10.0 MHz.

The second ion trap or ion guide is preferably arranged and adapted toreceive a beam or group of ions and to convert or partition the beam orgroup of ions such that a plurality or at least 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 separate packets of ionsare confined and/or isolated in the second ion trap or ion guide at anyparticular time. Each packet of ions is preferably separately confinedand/or isolated in a separate real axial potential well formed withinthe second ion trap or ion guide.

According to an embodiment the mass spectrometer preferably comprisesmeans arranged and adapted to urge at least some ions upstream and/ordownstream through or along at least 5%, 10%, 15%, 20%, 25%, 30%, 35%,40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% ofthe axial length of the second ion trap or ion guide in a mode ofoperation.

According to an embodiment the mass spectrometer further comprises thirdtransient DC voltage means arranged and adapted to apply one or moretransient DC voltages or potentials or one or more transient DC voltageor potential waveforms to the electrodes forming the second ion trap orion guide in order to urge at least some ions upstream and/or downstreamalong at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the axial length ofthe second ion trap or ion guide.

According to a less preferred embodiment the mass spectrometer mayfurther comprise AC or RF voltage means arranged and adapted to applytwo or more phase-shifted AC or RF voltages to electrodes forming thesecond ion trap or ion guide in order to urge at least some ionsupstream and/or downstream along at least 5%, 10%, 15%, 20%, 25%, 30%,35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100%of the axial length of the second ion trap or ion guide.

The mass spectrometer preferably further comprises means arranged andadapted in a mode of operation to maintain at least a portion of thesecond ion trap or ion guide at a pressure selected from the groupconsisting of: (i) >0.0001 mbar; (ii) >0.001 mbar; (iii) >0.01 mbar;(iv) >0.1 mbar; (v) >1 mbar; (vi) >10 mbar; (vii) >1 mbar; (viii)0.0001-100 mbar; and (ix) 0.001-10 mbar.

According to an embodiment the mass spectrometer preferably furthercomprises second acceleration means arranged and adapted to accelerateions into the second ion trap or ion guide wherein in a mode ofoperation at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of the ions are caused tofragment or react upon entering the second ion trap or ion guide.

The second acceleration means preferably accelerates ions from the ionmobility spectrometer or separator into the second ion trap or ionguide.

The mass spectrometer preferably comprises a control system arranged andadapted to switch or repeatedly switch the potential difference throughwhich ions pass prior to entering the second ion trap or ion guidebetween a relatively high fragmentation or reaction mode of operationwherein ions are substantially fragmented or reacted upon entering thesecond ion trap or ion guide and a relatively low fragmentation orreaction mode of operation wherein substantially fewer ions arefragmented or reacted or wherein substantially no ions are fragmented orreacted upon entering the second ion trap or ion guide. In therelatively high fragmentation or reaction mode of operation ionsentering the second ion trap or ion guide are preferably acceleratedthrough a potential difference selected from the group consisting of:(i) ≧10 V; (ii) ≧20 V; (iii) ≧30 V; (iv) ≧40 V; (v) ≧50 V; (vi) ≧60 V;(vii) ≧70 V; (viii) ≧80 V; (ix) ≧90 V; (x) ≧100 V; (xi) ≧110 V; (xii)≧120 V; (xiii) ≧130 V; (xiv) ≧140 V; (xv) ≧150 V; (xvi) ≧160 V; (xvii)≧170 V; (xviii) ≧180 V; (xix) ≧190 V; and (xx) ≧200 V. In the relativelylow fragmentation or reaction mode of operation ions entering the secondion trap or ion guide are preferably accelerated through a potentialdifference selected from the group consisting of: (i) ≦20 V; (ii) ≦15 V;(iii) ≦10 V; (iv) ≦5V; and (v) ≦1V.

According to an embodiment the mass spectrometer preferably furthercomprises an ion gate or deflection system arranged upstream and/ordownstream of the device arranged downstream of the first ion trap orion guide. The ion gate or deflection system preferably attenuates ionsexiting the device which have an undesired transit time through thedevice or an undesired ion mobility, mass to charge ratio or rate ofchange of ion mobility with electric field strength.

A first mass filter or mass analyser may be arranged upstream and/ordownstream of the first ion trap or ion guide. The first mass filter ormass analyser is preferably selected from the group consisting of: (i) aquadrupole rod set mass filter or mass analyser; (ii) a Time of Flightmass filter or mass analyser; (iii) a Wein filter; and (iv) a magneticsector mass filter or mass analyser. In a mode of operation the firstmass filter or mass analyser may be operated in a substantiallynon-resolving or ion guiding mode of operation. In another mode ofoperation the first mass filter or mass analyser may be scanned or amass to charge ratio transmission window of the first mass filter ormass analyser may be varied with time.

A second mass filter or mass analyser may be arranged upstream and/ordownstream of the second ion trap or ion guide. The second mass filteror mass analyser is preferably selected from the group consisting of:(i) a quadrupole rod set mass filter or mass analyser; (ii) a Time ofFlight mass filter or mass analyser; (iii) a Wein filter; and (iv) amagnetic sector mass filter or analyser. In a mode of operation thesecond mass filter or mass analyser may be operated in a substantiallynon-resolving or ion guiding mode of operation. In another mode ofoperation the second mass filter or mass analyser is preferably scannedor a mass to charge ratio transmission window of the second mass filteror mass analyser is preferably varied with time.

According to an embodiment in a mode of operation the first mass filteror mass analyser and/or the second mass filter or mass analyser may bescanned or a mass to charge ratio transmission window of the first massfilter or mass analyser and/or the second mass filter or mass analysermay be varied with time preferably in synchronism with the operation ofthe device or the ion mobility or rate of change of ion mobility withelectric field strength of ions emerging from and/or being transmittedto the device.

According to an embodiment in a mode of operation the first mass filteror mass analyser is preferably scanned or a mass to charge ratiotransmission window of the first mass filter or mass analyser ispreferably varied with time in synchronism with the operation of thesecond mass filter or mass analyser.

The mass spectrometer may comprise a collision, fragmentation orreaction device arranged and adapted to fragment ions by CollisionInduced Dissociation (“CID”).

According to a less preferred embodiment the mass spectrometer maycomprise a collision, fragmentation or reaction device selected from thegroup consisting of: (i) a Surface Induced Dissociation (“SID”)fragmentation device; (ii) an Electron Transfer Dissociationfragmentation device; (iii) an Electron Capture Dissociationfragmentation device; (iv) an Electron Collision or Impact Dissociationfragmentation device; (v) a Photo Induced Dissociation (“PID”)fragmentation device; (vi) a Laser Induced Dissociation fragmentationdevice; (vii) an infrared radiation induced dissociation device; (viii)an ultraviolet radiation induced dissociation device; (ix) anozzle-skimmer interface fragmentation device; (x) an in-sourcefragmentation device; (xi) an ion-source Collision Induced Dissociationfragmentation device; (xii) a thermal or temperature sourcefragmentation device; (xiii) an electric field induced fragmentationdevice; (xiv) a magnetic field induced fragmentation device; (xv) anenzyme digestion or enzyme degradation fragmentation device; (xvi) anion-ion reaction fragmentation device; (xvii) an ion-molecule reactionfragmentation device; (xviii) an ion-atom reaction fragmentation device;(xix) an ion-metastable ion reaction fragmentation device; (xx) anion-metastable molecule reaction fragmentation device; (xxi) anion-metastable atom reaction fragmentation device; (xxii) an ion-ionreaction device for reacting ions to form adduct or product ions;(xxiii) an ion-molecule reaction device for reacting ions to form adductor product ions; (xxiv) an ion-atom reaction device for reacting ions toform adduct or product ions; (xxv) an ion-metastable ion reaction devicefor reacting ions to form adduct or product ions; (xxvi) anion-metastable molecule reaction device for reacting ions to form adductor product ions; and (xxvii) an ion-metastable atom reaction device forreacting ions to form adduct or product ions.

According to an embodiment the collision, fragmentation or reactiondevice preferably forms at least part of the first ion trap or ion guideand/or the device and/or the second ion trap or ion guide. According toan alternative embodiment the collision, fragmentation or reactiondevice may be arranged upstream and/or downstream of the first ion trapor ion guide and/or the device and/or the second ion trap or ion guide.

The mass spectrometer preferably comprises an ion source. The ion sourceis preferably selected from the group consisting of: (i) an Electrosprayionisation (“ESI”) ion source; (ii) an Atmospheric Pressure PhotoIonisation (“APPI”) ion source; (iii) an Atmospheric Pressure ChemicalIonisation (“APCI”) ion source; (iv) a Matrix Assisted Laser DesorptionIonisation (“MALDI”) ion source; (v) a Laser Desorption Ionisation(“LDI”) ion source; (vi) an Atmospheric Pressure Ionisation (“API”) ionsource; (vii) a Desorption Ionisation On Silicon (“DIOS”) ion source;(viii) an Electron Impact (“EI”) ion source; (ix) a Chemical Ionisation(“CI”) ion source; (x) a Field Ionisation (“FI”) ion source; (xi) aField Desorption (“FD”) ion source; (xii) an Inductively Coupled Plasma(“ICP”) ion source; (xiii) a Fast Atom Bombardment (“FAB”) ion source;(xiv) a Liquid Secondary Ion Mass Spectrometry (“LSIMS”) ion source;(xv) a Desorption Electrospray Ionisation (“DESI”) ion source; (xvi) aNickel-63 radioactive ion source; (xvii) an Atmospheric Pressure MatrixAssisted Laser Desorption Ionisation (“AP-MALDI”) ion source; and(xviii) a Thermospray ion source.

The ion source may comprise a pulsed or continuous ion source.

The mass spectrometer preferably further comprises separation means forseparating molecules from a mixture of other molecules prior to beingionised. The separation means is preferably selected from the groupconsisting of: (i) High Performance Liquid Chromatography (“HPLC”); (ii)anion exchange; (iii) anion exchange chromatography; (iv) cationexchange; (v) cation exchange chromatography; (vi) ion pairreversed-phase chromatography; (vii) chromatography; (vii) singledimensional electrophoresis; (ix) multi-dimensional electrophoresis; (x)size exclusion; (xi) affinity; (xii) reverse phase chromatography;(xiii) Capillary Electrophoresis Chromatography (“CEC”); (xiv)electrophoresis; (xv) ion mobility separation; (xvi) Field AsymmetricIon Mobility Separation (“FAIMS”); and (xvi) capillary electrophoresis.

According to an embodiment the ion source is provided with an eluentover a period of time. The eluent is preferably separated from a mixtureby means of liquid chromatography or capillary electrophoresis.According to a less preferred embodiment the ion source may be providedwith an eluent over a period of time wherein the eluent has beenseparated from a mixture by means of gas chromatography.

The mass spectrometer preferably further comprises a mass analyser. Themass analyser is preferably arranged downstream of the second ion trapor ion guide. The mass analyser is preferably selected from the groupconsisting of: (i) a quadrupole mass analyser; (ii) a 2D or linearquadrupole mass analyser; (iii) a Paul or 3D quadrupole mass analyser;(iv) a Penning trap mass analyser; (v) an ion trap mass analyser; (vi) amagnetic sector mass analyser; (vii) Ion Cyclotron Resonance (“ICR”)mass analyser; (viii) a Fourier Transform Ion Cyclotron Resonance(“FTICR”) mass analyser; (ix) an electrostatic or orbitrap massanalyser; (x) a Fourier Transform electrostatic or orbitrap massanalyser; (xi) a Fourier Transform mass analyser; (xii) a Time of Flightmass analyser; (xiii) an orthogonal acceleration Time of Flight massanalyser; (xiv) an axial acceleration Time of Flight mass analyser; and(xv) a quadrupole rod set mass filter or mass analyser.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

providing a first ion trap or ion guide;

separating ions according to their ion mobility or rate of change of ionmobility with electric field strength in a device, the device beingarranged downstream of the first ion trap or ion guide;

providing a second ion trap or ion guide arranged downstream of thedevice; and

passing or transmitting ions from the second ion trap or ion guide tothe device.

According to an aspect of the present invention there is provided a massspectrometer comprising:

a device for separating ions according to their ion mobility or rate ofchange of ion mobility with electric field strength;

wherein in a mode of operation at a first time ions are passed in afirst direction through the device and wherein at a second later timeions are passed in second direction through the device, wherein thesecond direction is different or opposed to the first direction.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

separating ions according to their ion mobility or rate of change of ionmobility with electric field strength in a device; and

passing ions at a first time in a first direction through the device andpassing ions at a second later time in a second direction through thedevice, wherein the second direction is different or opposed to thefirst direction.

According to an aspect of the present invention there is provided a massspectrometer comprising:

a device for separating ions according to their ion mobility or rate ofchange of ion mobility with electric field strength;

an ion trap or ion guide which is arranged to receive ions emerging fromthe device and which are being transmitted in a first direction; and

acceleration means arranged and adapted to cause ions emerging from thedevice to be fragmented or to react upon entering the ion trap or ionguide so that a plurality of fragment, daughter, product or adduct ionsare formed;

wherein in a mode of operation at least some of the plurality offragment, daughter, product or adduct ions are transmitted or passedfrom the ion trap or ion guide to the device in a second direction whichis different from or opposed to the first direction.

According to an aspect of the present invention there is provided amethod of mass spectrometry comprising:

separating ions according to their ion mobility or rate of change of ionmobility with electric field strength in a device; and

providing an ion trap or ion guide which is arranged to receive ionsemerging from the device and which are being transmitted in a firstdirection;

accelerating ions emerging from the device so that the ions arefragmented or react upon entering the ion trap or ion guide so that aplurality of fragment, daughter, product or adduct ions are formed; and

transmitting or passing at least some of the plurality of fragment,daughter, product or adduct ions from the ion trap or ion guide to thedevice in a second direction which is different from or opposed to thefirst direction.

According to another aspect of the present invention there is provided amass spectrometer comprising:

a first ion trap or ion guide;

a device for separating ions according to their ion mobility or rate ofchange of ion mobility with electric field strength, the device beingarranged downstream of the first ion trap or ion guide;

a second ion trap or ion guide arranged downstream of the first ion trapor guide;

wherein in a mode of operation ions are passed from the first ion trapor ion guide to the device and onwards to the second ion trap or ionguide whereupon at least some of the ions or at least some fragment,daughter, product or adduct ions derived from the ions are then passedfrom the second ion trap or ion guide to the device and onwards to thefirst ion trap or ion guide.

According to another aspect of the present invention there is provided amethod of mass spectrometry comprising:

providing a first ion trap or ion guide;

providing a device for separating ions according to their ion mobilityor rate of change of ion mobility with electric field strength, thedevice being arranged downstream of the first ion trap or ion guide;

providing a second ion trap or ion guide arranged downstream of thefirst ion trap or guide; and

passing ions from the first ion trap or ion guide to the device andonwards to the second ion trap or ion guide; and then

passing at least some of the ions or at least some fragment, daughter,product or adduct ions derived from the ions from the second ion trap orion guide to the device and onwards to the first ion trap or ion guide.

According to the preferred embodiment a mass spectrometer is providedwhich comprises only a relatively few stages. However, the massspectrometer is preferably nonetheless capable of performing relativelycomplex experiments which conventionally would require a massspectrometer comprising a greater number of stages to perform. Forexample, a mass spectrometer according to an embodiment of the presentinvention comprising LC-IMS-MS stages is preferably able to performsimilar experiments to those which may be performed using a conventionalmass spectrometer comprising LC-IMS-IMS-MS or LC-IMS-CID-IMS-MS stages.

A mass spectrometer according to the preferred embodiment preferablycomprising a single ion mobility separation stage is preferably alsoable to perform particularly complex experiments which wouldconventionally require a mass spectrometer comprising, for example,LC-IMS-CID-IMS-CID-MS stages to perform wherein second generationfragment or daughter ions are produced and are subsequently massanalysed.

The conventional approach to designing a mass spectrometer has been toprovide multiple ion mobility separation and ion fragmentation stages inseries. Ions pass sequentially through multiple stages from one stage ofthe mass spectrometer to the next. The number of ion mobility separationand ion fragmentation stages which need to be provided is determined bythe desired capability of the mass spectrometer. The conventionalapproach leads to a mass spectrometer comprising a large number ofdiscrete stages and which is relatively lengthy and complex. The massspectrometer design is relatively inflexible and the range ofexperiments that can be performed by such a conventional massspectrometer is limited by the number and arrangement of the variousstages. A conventional mass spectrometer comprising a single ionfragmentation stage is not, for example, able to produce secondgeneration fragment or daughter ions. In addition when only part of thecapability of a mass spectrometer is utilised (e.g. an LC-IMS-MSanalysis is required using a mass spectrometer comprisingLC-IMS-CID-IMS-MS stages) then the extra stages are unnecessary and cancompromise performance. For example, the elution profile of an ionspecies leaving a first ion mobility separation region may not be ableto be measured directly since the ions may have to pass through anadditional ion mobility separation region before reaching an iondetector. Conventional mass spectrometers comprising numerous multiplestages in series also require a more complex calibration procedure andthis can lead to less certainty in the results.

A mass spectrometer according to the preferred embodiment preferablyenables a more compact and substantially more flexible mass spectrometerto be provided. A particularly preferred aspect of the present inventionis that ions in a mode of operation are passed back upstream at leastonce through a single ion mobility separation stage or section.

According to an embodiment a mass spectrometer is preferably providedcomprising an ionisation source and an ion mobility spectrometer orseparator comprising an RF ion guide wherein ions are confined near tothe central axis. Ions are preferably propelled along the length of theion mobility spectrometer or separator from one end to the other end ineither direction. The mass spectrometer preferably further comprises anion detector.

In a preferred embodiment ions are preferably propelled along the axisof the ion mobility spectrometer or separator first in one direction(e.g. downstream) and then preferably in the opposite or reversedirection (e.g. upstream). The ions are preferably separated accordingto their ion mobility in at least one pass through the length of the ionmobility spectrometer or separator. Each time ions are passed along orthrough the length of the ion mobility spectrometer or separator theions may or may not be separated according to their ion mobility.

In one embodiment the ion mobility spectrometer or separator maycomprise a drift tube comprising an RF ion guide wherein an axial DCvoltage gradient is preferably maintained along the length of the ionguide. The direction of the axial DC voltage gradient may preferably bereversed when it is desired to cause ions to separate according to theirion mobility in the reverse direction.

In another embodiment the ion mobility spectrometer or separator maycomprise an RF ion guide wherein one or more transient DC potentials orvoltages or DC potential or voltage waveforms are applied to theelectrodes of the ion guide. The one or more transient DC voltages orpotentials or DC voltage or potential waveforms are preferably initiallyapplied to the electrodes of the ion guide so that ions are urged in afirst (e.g. downstream) direction. The one or more transient DC voltagesor potentials or DC voltage or potential waveforms may then be appliedto the electrodes of the ion guide so as to urge ions in a secondopposite direction (e.g. upstream).

According to the preferred embodiment ions may be trapped in at leastone region, ion trap or ion guide. For example, a first ion trap may belocated upstream of an ion mobility spectrometer or separator. A secondion trap may be located downstream of the ion mobility spectrometer orseparator. Ions are preferably accumulated and trapped in either thefirst ion trap and/or the second ion trap before the ions are thenpreferably released and passed through the ion mobility spectrometer orseparator. In an embodiment ions are preferably trapped in the first iontrap or ion guide and/or the second ion trap or ion guide such that oneor more groups of ions are spatially separated along the central axis ofthe ion trap and such that the ions are fractionated or provided inseparate packets of ions which preferably remain isolated from eachother. One or more of the isolated packets of ions may then be retainedwithin the ion trap whilst one or more other packets of ions may bediscarded from the ion trap.

In one embodiment ions are preferably fragmented. Ions may be fragmentedin a region or ion trap arranged either upstream and/or downstream ofthe ion mobility spectrometer or separator. Ions may also be fragmentedeither before or after they have passed through the ion mobilityspectrometer or separator.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be described, byway of example only, and with reference to the accompanying drawings inwhich:

FIG. 1 shows an embodiment of the present invention wherein a first iontrap is provided upstream of an ion mobility spectrometer or separatorand a second ion trap is provided downstream of the ion mobilityspectrometer or separator to receive ions which emerge from the ionmobility spectrometer or separator;

FIG. 2 shows an ion mobility spectrum of a group of ions and theirassociated drift time through an ion mobility spectrometer or separator;

FIG. 3A shows the ion mobility spectrum as shown in FIG. 2 and indicatesthree drift time regions, FIG. 3B shows a mass spectrum of ions observedbetween drifts times O and time T1, FIG. 3C shows a mass spectrum ofions observed between drift times T1 and T2 and FIG. 3D shows a massspectrum of ions observed subsequent to drift time T2;

FIG. 4 shows an embodiment of the present invention wherein twoadditional electrode assemblies are provided and wherein the second iontrap or ion guide is located in a separate vacuum chamber;

FIG. 5 illustrates a preferred mode of operation wherein parent orprecursor ions are separated according to their ion mobility and arethen fragmented upon entering a second downstream ion trap, and whereinselected groups of resulting fragment or daughter ions are passedupstream through the ion mobility spectrometer or separator to betrapped in a first ion trap, whereupon the fragment or daughter ions arethen passed downstream through the ion mobility spectrometer orseparator and are separated according to their ion mobility;

FIG. 6 shows a further embodiment of the present invention wherein thefirst ion trap, the ion mobility spectrometer or separator and thesecond ion trap are each provided in separate vacuum chambers; and

FIG. 7 illustrates a preferred mode of operation wherein parent orprecursor ions are separated according to their ion mobility and arethen fragmented into first generation fragment ions upon entering asecond downstream ion trap, and wherein a selected group of firstgeneration fragment ions is passed upstream through the ion mobilityspectrometer or separator whereupon the first generation fragment ionsare separated according to their ion mobility and wherein the firstgeneration fragment ions are then fragmented into second generationfragment ions upon entering a first upstream ion trap.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

A preferred embodiment of the present invention will now be describedwith reference to FIG. 1. FIG. 1 shows a schematic arrangement of a massspectrometer according to an embodiment of the present inventioncomprising an ion source 1 and a first ion trap 2 or means ofcollecting, storing and releasing ions 2 arranged downstream of the ionsource 1. An ion mobility spectrometer or separator 3 is preferablyarranged downstream of the first ion trap 2. A second ion guide or iontrap 4 is preferably arranged downstream of the ion mobilityspectrometer or separator 3. The second ion guide or ion trap 4preferably comprises a second means of collecting, storing and releasingions. A mass analyser 5 is preferably arranged downstream of the secondion or ion trap 4 and the ion mobility separator or spectrometer 3.

The ion source 1 may comprise a pulsed ion source such as a LaserDesorption Ionisation (“LDI”) ion source, a Matrix Assisted LaserDesorption/Ionisation (“MALDI”) ion source or a Desorption/Ionisation onSilicon (“DIOS”) ion source. Alternatively, the ion source 1 maycomprise a continuous ion source 2 such as an Electrospray Ionisation(“ESI”) ion source, an Atmospheric Pressure Chemical Ionisation (“APCI”)ion source, an Electron Impact (“EI”) ion source, an AtmosphericPressure Photon Ionisation (“APPI”) ion source, a DesorptionElectrospray Ionisation (“DESI”) ion source, an Atmospheric PressureMALDI (“AP-MALDI”) ion source, a Chemical Ionisation (“CI”) ion source,a Fast Atom Bombardment (“FAB”) ion source, a Liquid Secondary Ion MassSpectrometry (“LSIMS”) ion source, a Field Ionisation (“FI”) ion sourceor a Field Desorption (“FD”) ion source. Other continuous orpseudo-continuous ion sources may also be used.

A differential pumping aperture 6 is preferably provided between the ionsource 1 and the first ion trap or ion guide 2. A differential pumpingaperture is also preferably provided between the second ion trap or ionguide 4 and the mass analyser 5. According to an embodiment the firstion trap or ion guide 2, the ion mobility spectrometer or separator 3and the second ion trap or ion guide 4 are provided in the same vacuumchamber.

A mass filter (not shown) such as a quadrupole rod set mass filter, aWein filter, a Time of Flight mass analyser or a magnetic sector massanalyser may optionally be provided between the ion source 1 and thefirst ion trap or ion guide 2. The mass filter may be arranged in a modeof operation to select certain parent or precursor ions for onwardtransmission to the first ion trap or ion guide 2 and to attenuate otherions.

Ions are preferably collected and stored in the first ion trap or ionguide 2. The first ion trap or ion guide 2 is preferably maintained at apressure between 10⁻⁴ mbar and 100 mbar, further preferably between 10⁻³and 10 mbar. The first ion trap or ion guide 2 preferably comprises anRF ion guide wherein ions are confined close to the central axis whenundergoing collisions with background gas molecules.

The first ion trap or ion guide 2 preferably comprises a stacked ring orion tunnel RF ion guide comprising a plurality of electrodes havingapertures through which ions are preferably transmitted in use. Oppositephases of an AC or RF voltage are preferably applied to neighbouring oradjacent ring electrodes so that ions are preferably radially confinedwithin the first ion trap or ion guide 2 by a radial pseudo-potentialwell. One or more transient DC potentials or voltages or DC potential orvoltage waveforms are preferably applied or superimposed to theelectrodes forming the first ion trap or ion guide 2 so that in a modeof operation ions are preferably urged along the length of the first ionguide or ion trap 2. Ions are preferably trapped in discrete real axialpotential wells which are preferably formed within the first ion guideor ion trap 2 and which are preferably translated or moved along thelength of the first ion guide or ion trap 2.

According to another embodiment the first ion trap or ion guide maycomprise a sandwich plate RF ion trap or ion guide comprising aplurality of electrodes arranged generally in the plane of iontransmission. AC or RF voltages and optionally DC voltages may beapplied to the electrodes of the ion trap or ion guide in order toconfine ions radially within the ion trap or ion guide.

The first ion trap or ion guide 2 may alternatively comprise an ionfunnel ion guide comprising a plurality of electrodes each having anaperture through which ions are transmitted in use. The diameter or sizeof the apertures of the electrodes preferably taper in one directionalong the length of the ion funnel ion guide.

According to another embodiment the first ion guide or ion trap 2 maycomprise a quadrupole, hexapole, octapole or higher order multipole rodset ion guide. The first ion trap or ion guide 2 may be segmentedaxially into a plurality of axial segments.

The first ion trap or ion guide 2 is preferably arranged to store ionsreceived from the ion source 1 and to release ions in one or more pulsesinto the ion mobility spectrometer or separator 3 which is preferablyarranged downstream of the first ion trap or ion guide 2. A plate orelectrode may be provided (not shown) at the exit of the first ion trapor ion guide 2. The plate or electrode may be maintained at a potentialsuch that a potential barrier is preferably created which preferablyprevents ions from exiting the first ion trap or ion guide 2. Forpositive ions the plate or exit electrode may be maintained at apotential of approximately +10 V with respect to the DC potential atwhich the other electrodes forming the first ion trap or ion guide 2 aremaintained in order to prevent ions from exiting the first ion guide orion trap 2. If the potential on the plate or electrode at the exit ofthe first ion guide or ion trap 2 is momentarily lowered to 0 V, or lessthan 0 V, with respect to the potential at which the other electrodesforming the first ion trap or ion guide 2 are maintained, then ions willpreferably be released from the first ion guide or ion trap 2 in a pulseinto or towards the ion mobility spectrometer or separator 3.

According to an embodiment the first ion trap or ion guide 2 preferablycomprises a plurality of electrodes wherein the apertures of theelectrodes are preferably all the same size. In other embodiments atleast 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes mayhave apertures which are substantially the same size. Adjacentelectrodes are preferably connected to opposite phases of an AC or RFsupply so that a radial pseudo-potential well is created which acts toconfine ions radially within the first ion trap or ion guide 2.

One or more transient DC potentials or voltages or DC potential orvoltage waveforms are preferably superimposed onto the electrodesforming the first ion trap or ion guide 2 in a mode of operation. Theone or more transient DC voltages or potentials or DC potential orvoltage waveforms are preferably applied to the electrodes of the firstion trap or ion guide 2 so that one or more real potential barriers areformed or created along the length of the first ion trap or ion guide 2.The one or more transient DC voltages or potentials or DC potential orvoltage waveforms are preferably progressively applied to a successionof electrodes of the first ion trap or ion guide 2 such that the one ormore real potential barriers preferably move along or are translatedalong the axis of the first ion trap or ion guide 2. Ions may in a modeof operation be propelled or urged in a downstream direction towards theion mobility spectrometer or separator 3 and the mass analyser 5. Inanother mode of operation ions may be urged in an opposite directioni.e. upstream towards the ion source 1.

The first ion trap or ion guide 2 is preferably provided in a vacuumchamber that is preferably maintained, in use, at a pressure within therange 0.001-10 mbar. The gas pressure within the first ion trap or ionguide 2 is preferably sufficient to impose collisional damping of ionmotion but is preferably not sufficient so as to impose excessiveviscous drag upon the movement of ions. The amplitude and averagevelocity of the one or more potential barriers which are preferablytranslated along the length of the first ion trap or ion guide 2 in amode of operation is preferably set such that ions are preferably unableto slip over the one or more potential hills or barriers. Ions aretherefore preferably transported ahead of each potential barrier whichis translated along the length of the first ion trap or ion guide 2regardless of the mass, mass to charge ratio or ion mobility of the ion.

The ion mobility spectrometer or separator 3 which is preferablyprovided downstream of the first ion guide or ion trap preferablycomprises a device which in a mode of operation causes ions to becometemporally separated according to their ion mobility. The ion mobilityspectrometer or separator 3 may comprise one of several different forms.

The ion mobility spectrometer or separator 3 may comprise a drift tubewherein a number of guard rings are distributed within the drift tube.The guard rings are preferably interconnected by equivalent valuedresistors and are preferably connected to a DC voltage source. A linearDC voltage gradient is preferably generated or maintained along thelength of the drift tube. According to this embodiment ions may not beconfined radially within the ion mobility spectrometer or separator 3.

According to another embodiment the ion mobility spectrometer orseparator 3 may comprise a plurality of ring, annular or plateelectrodes. The electrodes preferably each have an aperture thereinthrough which ions are preferably transmitted in use. The apertures arepreferably all the same size and are preferably circular. In otherembodiments at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of theelectrodes preferably have apertures that are substantially the samesize or area.

The ion mobility spectrometer or separator 3 may comprise a plurality ofelectrodes arranged in a discrete vacuum chamber. The ion mobilityspectrometer or separator 3 preferably has a length of between 100 mmand 200 mm. The ion mobility spectrometer or separator 3 is preferablyprovided in a vacuum chamber that is preferably maintained, in use, at apressure within the range 0.1-10 mbar.

Alternate electrodes forming the ion mobility spectrometer or separator3 are preferably coupled to opposite phases of an AC or RF voltagesupply so that ions are preferably confined radially within the ionmobility spectrometer or separator in a radial pseudo-potential well.The AC or RF voltage supply preferably has a frequency within the range0.1-3.0 MHz, preferably 0.3-2.0 MHz, further preferably 0.5-1.5 MHz.

According to an embodiment the electrodes comprising the ion mobilityspectrometer or separator 3 may be interconnected via resistors to a DCvoltage supply which may, for example, comprise a 400 V supply. Theresistors interconnecting the electrodes forming the ion mobilityspectrometer or separator 3 may be substantially equal in value so thata linear axial DC voltage gradient is preferably maintained along thelength of the ion mobility spectrometer or separator 3.

According to an embodiment the DC voltage gradient maintained along thelength of the ion mobility spectrometer or separator 3 may have alinear, non-linear, continuous or stepped profile. The DC voltagegradient may according to an embodiment be arranged in a mode ofoperation so as to propel, drive, force or urge ions in a downstreamdirection towards the mass analyser 5. The direction of the DC voltagegradient may be switched, or reversed in use, so that ions may be urgedin a mode of operation in the opposite direction e.g. in an upstreamdirection towards the ion source 1. The AC or RF voltage which ispreferably applied to the electrodes forming the ion mobilityspectrometer or separator 3 is preferably superimposed upon the DCvoltage applied to the electrodes and preferably serves to cause ions tobe confined radially within the ion mobility spectrometer or separator 3within a radial pseudo-potential well.

According to a preferred embodiment the ion mobility spectrometer orseparator 3 preferably comprises an ion guide comprising a plurality ofelectrodes each having an aperture through which ions are transmitted.One or more transient DC voltages or potentials or one or more transientDC voltage or potential waveforms are preferably applied to theelectrodes. The apertures of the electrodes forming the ion mobilityspectrometer or separator 3 are preferably all the same size. In otherembodiments at least 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of theelectrodes have apertures that are substantially the same size. Adjacentelectrodes are preferably connected to the opposite phases of an AC orRF supply so that ions are confined radially within the ion mobilityspectrometer or separator.

The one or more transient DC voltages or potentials or one or moretransient DC voltage or potential waveforms which are preferably appliedto the electrodes of the ion mobility spectrometer or separator 3preferably cause one or more real potential hills or barriers to becreated which are then preferably translated or moved along the axis ofthe ion mobility spectrometer or separator 3. The one or more transientDC voltages or potentials or DC voltage or potential waveforms arepreferably progressively applied to a succession of electrodes of theion mobility spectrometer or separator 3 in such a way that one or morereal potential hills or barriers preferably move along or are translatedalong the axis or length of the ion mobility spectrometer or separator3. In a mode of operation ions are preferably driven or urged downstreamtowards the mass analyser 5. In another mode of operation ions arepreferably driven or urged in a reverse direction upstream towards theion source 1.

The ion mobility spectrometer or separator 3 is preferably provided in avacuum chamber that is preferably maintained, in use, at a pressurewithin the range 0.1-10 mbar. The presence of gas within the ionmobility spectrometer or separator 3 preferably imposes a viscous dragupon the movement of ions. The amplitude and average velocity of the oneor more real potential hills or barriers which are preferably formed andtranslated along the length of the ion mobility spectrometer orseparator 3 is preferably arranged to be such that some ions will slipover the one or more potential hills or barriers as they are translatedalong the length of the ion mobility spectrometer or separator 3. Thelower the mobility of an ion the more likely it is that the ion willslip over a potential hill or barrier which is being translated alongthe length of the ion mobility spectrometer or separator 3. As a resultions having different ion mobilities will preferably be transported atdifferent velocities or rates along and through the length of the ionmobility spectrometer or separator 3 and will therefore preferably beseparated according to their ion mobility.

The typical drift times of ions through the preferred ion mobilityspectrometer or separator 3 may be of the order of 2-50 ms. According toa preferred embodiment ions may take between 5 and 20 ms to pass throughor along the length of the ion mobility spectrometer or separator 3.

According to the preferred embodiment ions preferably exit the ionmobility spectrometer or separator 3 and then preferably pass to or arereceived by a second ion trap or ion guide 4 which is preferablyarranged downstream of the ion mobility spectrometer or separator 3. Thesecond ion trap or ion guide 4 is preferably substantially similar tothe first ion trap or ion guide 2 arranged upstream of the ion mobilityspectrometer or separator 3. The second ion trap or ion guide 4preferably comprises a stacked ring or ion tunnel RF ion guidecomprising a plurality of electrodes having apertures through which ionsare transmitted in use. Opposite phases of an AC or RF voltage arepreferably applied to neighbouring electrodes of the second ion trap orion guide 4 so that ions are preferably confined radially within thesecond ion trap or ion guide 4 within a radial pseudo-potential well.

One or more transient DC voltages or potentials or DC voltage orpotential waveforms are preferably applied to the electrodes of thesecond ion trap or ion guide 4 in order to urge ions along the length ofthe second ion guide or ion trap 4. Ions are preferably trapped indiscrete real axial potential wells within the second ion trap or ionguide 4. In a mode of operation the real axial potential wells may betranslated in a downstream direction towards the mass analyser 5. Inanother mode of operation the real axial potential wells formed withinthe second ion trap or ion guide 4 may be translated in a reversedirection so that ions are preferably translated in an upstreamdirection and pass to the ion mobility spectrometer or separator 3. Inthis mode of operation the ion mobility spectrometer or separator thenpreferably passes the ions back further upstream to the first ion guideor ion trap 2.

According to a less preferred embodiment the second ion trap or ionguide 4 may comprise an alternative form of ion guide such as an AC orRF ion guide or ion trap comprising a plurality of planar, plate or meshelectrodes arranged generally in the plane of ion travel. AC or RFvoltages and optionally DC voltages may be applied to the electrodes ofthe ion guide or ion trap in order to confine ions radially within theion trap or ion guide.

Other embodiments are contemplated wherein the second ion trap or ionguide 4 may comprise an ion funnel ion guide comprising a plurality ofelectrodes having apertures. The diameter or size of the aperturespreferably tapers in size along the length of the ion trap or ion guide.

According to another embodiment the second ion trap or ion guide 4 maycomprise a quadrupole, hexapole, octapole or other higher ordermultipole rod set ion guide. The second ion trap or ion guide 4 may beaxially segmented into a plurality of axial segments.

The apertures of the electrodes forming the second ion trap or ion guide4 are preferably all the same size. In other embodiments at least 60%,65%, 70%, 75%, 80%, 85%, 90% or 95% of the electrodes have apertureswhich are substantially the same size. The second ion trap or ion guide4 is preferably provided in a vacuum chamber that is preferablymaintained, in use, at a pressure within the range 0.001-10 mbar.

The second ion trap or ion guide 4 may, in a mode of operation, bearranged to store ions and may then release ions in pulses or packets. Aplate or electrode (not shown) may be arranged at the exit of the secondion trap or ion guide 4. The plate or electrode may be maintained at apotential such that a potential barrier is preferably created whichsubstantially prevents ions from exiting the second ion trap or ionguide 4. If the potential on the plate or electrode at the exit of thesecond ion trap or ion guide 4 is momentarily lowered then ions may bereleased in a pulse from the second ion trap or ion guide 4.

According to the preferred embodiment a mass analyser 5 is preferablyarranged downstream of the second ion guide or ion trap 4. The massanalyser 5 preferably comprises an orthogonal acceleration Time ofFlight mass analyser. Alternatively, the mass analyser 5 may comprise anaxial acceleration Time of Flight mass analyser, a quadrupole rod setmass filter or mass analyser, a 3D quadrupole ion trap, a linearquadrupole ion trap, a magnetic sector mass analyser, an Ion CyclotronResonance mass analyser or an orbitrap mass analyser. The mass analyser5 may also comprise variations of the aforementioned types of massanalyser which employ Fourier Transforms of mass dependant resonancefrequencies and any combination thereof.

According to an embodiment of the present invention ions are preferablyproduced in the ion source 1 upstream of the first trap or ion guide 2.The ions are then preferably accumulated and stored in the first iontrap or ion guide 2. A group of ions is then preferably periodicallyreleased from the first ion trap or ion guide 2 and the ions preferablypass into the ion mobility spectrometer or separator 3. The ion mobilityspectrometer or separator 3 is preferably arranged to receive the groupof ions and preferably separates the ions according to their ionmobility. The ions preferably progress along the central axis of the ionmobility spectrometer or separator 3 and are temporally separatedaccording to their ion mobility.

FIG. 2 shows an ion mobility spectrum of a number of fragment ions whichresulted from the fragmentation of the doubly protonated ion (M+2H)²⁺having a mass to charge ratio 785.8 and which was derived from thepeptide Glu-Fibrinopeptide B. As can be seen from FIG. 2, ions havingrelatively low mass to charge ratios take a relatively short period timeto drift or pass along or through the ion mobility spectrometer orseparator 3 whereas ions having a relatively high mass to charge ratiotake a substantially longer time to drift or pass along or through theion mobility spectrometer or separator 3.

The ions exiting the ion mobility spectrometer or separator 3 arepreferably received by or into the second ion trap or ion guide 4. Thesecond ion trap or ion guide 4 is preferably arranged to collect andisolate one or more components, fractions or packets of ions which havebeen separated by the ion mobility spectrometer or separator 3 and whichpreferably emerge from the ion mobility spectrometer or separator 3 atdifferent times. The second ion trap or ion guide 4 preferably comprisesan ion guide comprising a plurality of electrodes having apertures andwherein one or more transient DC voltages or potentials or DC voltage orpotential waveforms is applied to the electrodes in a mode of operation.The one or more transient DC voltages or potentials or DC voltage orpotential waveforms applied to the electrodes of the second ion trap orion guide 4 is preferably synchronised with the release of ions from thefirst ion trap or ion guide 2. Preferably, some or all of the ions thathave been separated by the ion mobility spectrometer or separator 3according to their ion mobility are received by the second ion trap orguide 4 and separate packets of ions are preferably trapped withinseparate portions, sections or axial trapping regions formed within thesecond ion trap or ion guide 4. For example, ions that arrive at thesecond ion trap or ion guide 4 before a certain first drift time T1 maybe arranged to be collected or trapped within a first series of realaxial potential wells formed or created within the second ion trap orion guide 4. Ions that arrive at the second ion trap or ion guide 4after the first drift time T1 and before a second later drift time T2may be arranged to be collected or trapped within a second differentseries of real axial potential wells formed or created within the secondion trap or ion guide 4. Ions that arrive at the second ion trap or ionguide 4 after the second drift time T2 may be arranged to be collectedor trapped within a third yet further different series of real axialpotential wells formed or created within the second ion trap or ionguide 4.

FIGS. 3A-3D illustrate the different components, fractions or packets ofions which emerge from the ion mobility spectrometer or separator 3 atdifferent times. FIG. 3A shows an ion spectrum of the various differentfragment ions as illustrated in FIG. 2 and indicates two drift times T1and T2. FIG. 3B shows a mass spectrum of ions which emerge from the ionmobility spectrometer or separator 3 between drift times 0 and T1 andwhich have relatively low mass to charge ratios. FIG. 3C shows a massspectrum of ions which emerge from the ion mobility spectrometer orseparator 3 between drift times T1 and T2 and which have intermediatemass to charge ratios. FIG. 3D shows a mass spectrum of ions whichemerge from the ion mobility spectrometer or separator 3 subsequent todrift time T2 and which have relatively high mass to charge ratios. Itwill be appreciated that ions of interest having a specific drift timethrough the ion mobility spectrometer or separator 3 are preferablyarranged to be collected and trapped in one or more specific real axialpotential well(s) formed or created within the second ion trap or ionguide 4. The ions are preferably isolated from other ions which havedifferent drift times through the ion mobility spectrometer or separator3.

Once ions have been received and trapped within a series of separatereal axial potential wells formed or created within the second ion trapor ion guide 4, the transient DC voltages or potentials which arepreferably applied to the electrodes of the ion mobility spectrometer orseparator 3 may then be applied in the opposite direction so as to urgeions in the opposite direction i.e. the real axial potential wells maybe translated in an upstream direction back towards the ion source 1.The axial potential wells formed within the second ion trap or ion guide4 are preferably also translated in the opposite direction i.e. in adirection back towards the ion source 1.

According to an embodiment ions trapped in one or more axial potentialwells within the second ion trap or ion guide 4 which are not ofpotential interest may be discarded by, for example, temporarilyremoving the AC or RF voltage applied to the electrodes adjacent the oneor more axial potential wells in question so that the ions within theseone or more axial potential wells are now no longer confined radially.The ions are therefore allowed to disperse and are effectively lost.Alternatively, ions which are not of interest may be allowed to passback into the ion mobility spectrometer or separator 3 but may then bediscarded within the ion mobility spectrometer or separator 3. Ions maybe discarded within the ion mobility spectrometer or separator 3 bytemporarily removing the AC or RF voltage applied to some of theelectrodes of the ion mobility spectrometer or separator 3 or a sectionof the ion mobility spectrometer or separator 3 so that ions which arenot of interest are no longer confined radially within the ion mobilityspectrometer or separator 3. These ions are then allowed to disperse andare effectively lost. Other alternative means by which the ions may bediscarded either within the ion mobility spectrometer or separator 3and/or the first ion trap or ion guide 2 and/or the second ion trap orion guide 4 are also contemplated.

According to an embodiment a first group of ions which are of potentialinterest and which are trapped in an axial potential well within thesecond ion trap or ion guide 4 are preferably released from the secondion trap or ion guide 4 in an upstream direction towards the ionmobility spectrometer or separator 3. The ions are preferably arrangedto pass through the ion mobility spectrometer or separator 3 which in amode of operation may be arranged to operate in an ion guide only modeof operation so that ions are onwardly transmitted through the ionmobility spectrometer or separator 3 without being separated accordingto their ion mobility. Once the ions have passed through the ionmobility spectrometer or separator 3 the ions are then preferablycollected or trapped in one or more real axial potential wells which arepreferably formed or created within the first ion trap or ion guide 2. Asecond group of ions trapped in the next axial potential well within thesecond ion trap or ion guide 4 may then preferably be released from thesecond ion trap or ion guide and this group of ions may then preferablybe arranged to pass in an upstream direction into the ion mobilityspectrometer or separator 3. The second group of ions may then alsopreferably be arranged to pass through the ion mobility spectrometer orseparator 3 without being separated according to their ion mobility. Thesecond group of ions is then preferably collected and trapped in one ormore separate real axial potential wells formed or created within thefirst ion trap or ion guide 2. The process may be repeated multipletimes so that multiple packets of ions are preferably transferred fromthe second ion trap or ion guide to the first ion trap or ion guide 2via the ion mobility spectrometer or separator 3. Packets of ions maythen preferably be released in turn from the first ion trap or ion guide2 such that ions preferably pass back through the ion mobilityspectrometer or separator 3 and are preferably further separatedaccording to their ion mobility.

According to a preferred aspect of the present invention ions may bepassed back and forth through the ion mobility spectrometer or separator3 a plurality of times as required. Once ions have been sufficientlyseparated according to their ion mobility the ions are then preferablyonwardly transmitted or transported by the second ion trap or ion guide4 (which preferably operates in a non-trapping or ion guide only mode ofoperation) to the mass analyser 5.

According to an embodiment the potential difference which is preferablymaintained between the ion mobility spectrometer or separator 3 and thesecond ion guide or ion trap 4 may in a mode of operation be increasedwith time such that ions are induced to fragment in an optimum manner asthey are accelerated out of the exit of the ion mobility spectrometer orseparator 3 and into the second ion trap or guide 4. In this mode ofoperation the ions are preferably caused to fragment or react uponentering the second ion guide or ion trap 4. The resulting fragment ordaughter ions are preferably trapped in one or more real axial potentialwells formed or created within the second ion trap or guide 4. Fragmentor daughter ions which correspond to different parent or precursor ionswhich emerged from the ion mobility spectrometer or separator 3 atdifferent times are preferably collected and isolated in separate realaxial potential wells within the second ion trap or ion guide 4.

Once all parent or precursor ions have emerged from the ion mobilityspectrometer or separator 3 and have been fragmented into a plurality offragment or daughter ions, then all the fragment or daughter ionscorresponding to a particular parent or precursor ion may thenpreferably be separated according to their ion mobility by passing thegroup of fragment or daughter ions in the reverse direction backupstream to the ion mobility spectrometer or separator 3. The fragmentor daughter ions are then preferably separated according to their ionmobility as they pass upstream through the ion mobility spectrometer orseparator 3 towards the first ion trap or ion guide 2. Alternatively,the fragment or daughter ions may simply be transported or guidedthrough the ion mobility spectrometer or separator 3 without beingseparated according to their ion mobility i.e. the ion mobilityspectrometer or separator 3 may be operated in an ion guiding only modeof operation.

The process of separating ions into ion mobility fractions, fragmentingthe ions which emerge from the ion mobility spectrometer or separator 3and trapping and isolating one or more fractions of fragment or daughterions may be repeated a number of times. As a result second, third,fourth and higher generation fragment, daughter, product or adduct ionsmay be produced by varying the number passes of ions through the ionmobility spectrometer or separator 3 and varying the number offragmentation cycles. At the end of each cycle of operation ions exitingthe ion mobility spectrometer or separator 3 are preferably transportedby the second ion trap or ion guide 4 to the mass analyser 5 forsubsequent mass analysis.

Another embodiment of the present invention is shown in FIG. 4.According to this embodiment an electrode assembly 7 is preferablyprovided between the first ion trap or ion guide 2 and the ion mobilityspectrometer or separator 3. An electrode assembly 7 is also preferablyprovided between the ion mobility spectrometer or separator 3 and thesecond ion trap or ion guide 4.

One or both of the electrode assemblies 7 preferably function as adeflection system to divert ions away from the central axis so that ionsare then effectively lost to the system. According to another embodimentone or both of the electrode assemblies 7 may function as an ion gatewhich allows ions to pass through the ion gate in a mode of operationand which preferably prevent ions from passing through the ion gate inanother mode of operation. The ion gate may function by applying asuitable potential to the electrode assembly 7 so that a potentialbarrier exists which substantially prevents ions from passing beyond thepotential barrier. The potential barrier can then be removed for acontrolled period of time to allow certain ions to pass therethrough.

One or both of the electrode assemblies 7 are preferably capable ofbeing switched quickly between the two modes of operation. One or bothof the electrode assemblies 7 can preferably be switched quickly enoughto allow only some ions which have been separated according to their ionmobility by the ion mobility spectrometer or separator 3 to pass and toprevent or attenuate other ions which are emerging from the ion mobilityspectrometer or separator 3. With reference back to FIG. 3, an electrodeassembly 7 provided downstream of the ion mobility spectrometer orseparator 3 may, for example, be arranged to have a zero or 0%transmission efficiency between drift times 0 to T1 in order to block orattenuate ions which emerge from the ion mobility spectrometer orseparator 3 during these times. The electrode assembly 7 may then beswitched so as to have a full or 100% transmission efficiency betweendrift times T1 and T2 in order to transmit all ions which emerge fromthe ion mobility spectrometer or separator 3 between these two times.The electrode assembly 7 may then be switched back to have a zero or 0%transmission efficiency for the remainder of the ion mobility separationcycle in order to block or attenuate ions which emerge from the ionmobility spectrometer or separator 3 after drift time T2. As a resultthe second ion trap or ion guide 4 will only receive and trap ions whichwere transmitted through the ion mobility spectrometer or separator 3between drift times T1 and T2 and which therefore have intermediate massto charge ratios.

An electrode assembly 7 may also be placed at the entrance of the ionmobility spectrometer or separator 3 as shown in FIG. 4. This enablesdrift time selection to be performed when ions are transmitted backupstream through the ion mobility spectrometer separator 3 towards thefirst ion trap or ion guide 2. Various alternative systems of removingor attenuating ions as they emerge from the ion mobility spectrometer orseparator 3 prior to entering into the first ion trap or ion guide 2and/or the second ion trap or ion guide 4 are also contemplated.

According to an embodiment a further differential pumping aperture 6 maybe provided between the ion mobility spectrometer or separator 3 and thesecond ion trap or ion guide 4 as shown in FIG. 4. The furtherdifferential pumping aperture 6 in combination with the differentialpumping aperture 6 arranged between the second ion trap or ion guide 4and the mass analyser 5 preferably allows the second ion trap or ionguide 4 to be maintained at a substantially lower pressure than that ofthe ion mobility spectrometer or separator 3. According to an embodimentthe ion mobility spectrometer or separator 3 may be maintained at apressure in the range 0.1 mbar to 10 mbar. The second ion trap or ionguide 4 may, in contrast, be maintained at a relatively lower pressurein the range 0.001 to 0.1 mbar. By maintaining the second ion trap orion guide 4 at a lower pressure than that of the ion mobilityspectrometer or separator 3 the second ion trap or ion guide 4 may beused more effectively to induce fragmentation of ions by CollisionInduced Decomposition than if it were maintained at the same relativelyhigh pressure as the ion mobility spectrometer or separator 3. The massanalyser 5 is preferably maintained at a relatively low pressure <10⁻⁴mbar.

The ion mobility spectrometer or separator 3 may in a mode of operationbe arranged to operate as an ion guide so as to transmit ions eitherupstream towards the first ion trap or ion guide 2 or downstream towardsthe second ion trap or ion guide 4 without substantially separating theions according to their ion mobility. This may according to oneembodiment be achieved by, for example, lowering the gas pressure withinthe ion mobility spectrometer or separator 3 to a pressure of 0.01 mbaror less.

According to an embodiment one or more transient DC voltages orpotentials or DC potential or voltage waveforms may be applied to theelectrodes of the ion mobility spectrometer or separator 3 in order tocause a plurality of real axial potential wells or barriers to becreated which preferably act to transport or translate ions along thelength of the ion mobility spectrometer or separator 3 without causingthe ions to be separated according to their ion mobility. According tothis mode of operation the amplitude of the one or more transient DCvoltages or potentials or potential or voltage waveforms which ispreferably applied to the electrodes of the ion mobility spectrometer orseparator 3 is preferably increased so that ions are no longer able toslip over the crest of the one or more potential hills as they aretranslated along the length of the ion mobility spectrometer orseparator 3. Additionally or alternatively the velocity or rate at whichthe one or more transient DC potentials or voltages or DC potential orvoltage waveforms are applied to the electrodes of the ion mobilityspectrometer or separator 3 may be reduced.

In an embodiment the ion mobility spectrometer or separator 3 may beswitched between a mode of operation wherein ions are separatedaccording to their ion mobility and a mode of operation wherein ions arenot substantially separated according to their ion mobility. This may beachieved by a combination of switching the gas pressure and/or alteringthe amplitude of the one or more transient DC voltages or potentialsapplied to the electrodes and/or by altering the velocity or rate atwhich the one or more transient DC voltages or potentials are applied tothe electrodes of the ion mobility spectrometer or separator 3.

FIG. 5 illustrates a mode of operation wherein ions travel back andforth through the ion mobility spectrometer or separator 3 and whereinions are also fragmented. Ions are preferably separated according totheir ion mobility during some passes through the ion mobilityspectrometer or separator 3 but are preferably not separated accordingto their ion mobility during other passes through the ion mobilityspectrometer or separator 3.

The particular mode of operation shown in FIG. 5 will now be describedin more detail. As shown in step (a) of FIG. 5, parent or precursor ionsare preferably held initially within the first ion trap or ion guide 2.The parent or precursor ions are then preferably released from the firstion trap or ion guide 2 and preferably pass to the ion mobilityspectrometer or separator 3. The parent or precursor ions are thenpreferably separated according to their ion mobility as the parent orprecursor ions pass downstream through the ion mobility spectrometer orseparator 3 as shown in step (b). The parent or precursor ions are thenpreferably accelerated as they reach the exit of the ion mobilityspectrometer or separator 3 out from the ion mobility spectrometer orseparator 3 and into the second ion trap or ion guide 4 such that theparent or precursor ions are preferably caused to fragment into firstgeneration fragment ions upon entering the second ion trap or ion guide4. The resulting first generation fragment, daughter, product or adductions are then preferably collected and isolated in a plurality ofseparate real axial potential wells which are preferably created withinthe second ion trap or ion guide 4 as shown in step (c). According to anembodiment all the first generation fragment ions resulting from thefragmentation of a particular parent or precursor ion are preferablytrapped within the same real axial potential well within the second ionguide or ion trap 4. Fragment or daughter ions resulting from thefragmentation of other parent or precursor ions which subsequentlyemerge from the ion mobility spectrometer or separator 3 are preferablytrapped in separate or different real axial potential wells createdwithin the second ion guide or ion trap 4.

Once all the parent or precursor ions emerging from the ion mobilityspectrometer or separator 3 have been fragmented upon entering thesecond ion guide or ion trap 4 and the resulting fragment or daughterions have been trapped in separate real axial potential wells which arepreferably translated downstream along the length of the second ion trapor ion guide 4, the real axial potential wells containing the separatepackets of fragment ions within the second ion trap or ion guide 4 arepreferably held stationary. Ions within one or more of the real axialpotential wells may then be discarded as shown in step (d). The axialpotential wells comprising the remaining packets of fragment ions arethen preferably translated in an upstream direction along the length ofthe second ion trap or ion guide 4. The packets of ions are thenpreferably released from the second ion guide or ion trap 4 as a seriesof packets of ions. The packets of ions are then preferably transportedin an upstream direction through the ion mobility spectrometer orseparator 3 as shown in steps (e) and (f) towards the first ion trap orion guide 2. As the fragment ions are transmitted back through the ionmobility spectrometer or separator 3 the fragment ions are preferablynot separated according to their ion mobility as they pass upstreamthrough the ion mobility spectrometer or separator 3. Instead, the ionmobility spectrometer or separator 3 is preferably operated in an ionguiding only mode of operation. Each packet of fragment ions ispreferably trapped in a separate real axial potential well which ispreferably translated along the length of the ion mobility spectrometeror separator 3. The various separate packets of fragment ions are thenpreferably received by the first ion trap or ion guide 2 and thefragment ions are preferably retained or isolated in separate real axialpotential wells which are preferably formed or created within the firstion trap or ion guide 2 as shown in step (g).

The real axial potential wells or trapping regions provided in the firstion trap or ion guide 2 are then preferably moved or translated backdownstream such that a first packet of fragment ions in a first axialpotential well in the first ion trap or ion guide 2 is preferablyreleased back into or towards the ion mobility spectrometer or separator3. The first packet of fragment, daughter, product or adduct ions isthen preferably separated according to their ion mobility as thefragment or daughter ions pass downstream through the ion mobilityspectrometer or separator 3 towards the second ion trap or ion guide 4as shown in step (h).

The fragment, daughter, product or adduct ions are preferably separatedaccording to their ion mobility and preferably exit the ion mobilityspectrometer or separator 3 and enter the second ion trap or ion guide4. The ions are then preferably escorted or pass through the second iontrap or ion guide 4 and preferably pass to the mass analyser 5 forsubsequent mass analysis. A second packet of fragment, daughter, productor adduct ions is then preferably released from the first ion trap orion guide 2 into the ion mobility spectrometer or separator 3. Thesecond packet of fragment, daughter, product or adduct ions is thenpreferably separated according to their ion mobility as the fragment ordaughter ions pass downstream through the ion mobility spectrometer orseparator 3 towards the second ion trap or ion guide 4. The fragment,daughter, product or adduct ions are then preferably received by thesecond ion trap or ion guide 4 and are preferably onwardly transmittedto the mass analyser 5.

FIG. 6 shows a similar embodiment to that shown in FIG. 4 except that anadditional stage of differential pumping 6 is preferably providedbetween the first ion trap or ion guide 2 and the ion mobilityspectrometer or separator 3. This allows the first ion trap or ion guide2 to be maintained at a relatively lower pressure than that of the ionmobility spectrometer or separator 3. The ion mobility spectrometer orseparator 3 may, for example, be maintained at a pressure in the range0.1 mbar to 10 mbar whereas the first ion trap or ion guide 2 maypreferably be maintained at a relatively lower pressure in the range of0.001 to 0.1 mbar. Similarly, the second ion trap or ion guide 4 mayalso be maintained at a pressure in the range of 0.001 to 0.1 mbar whichis also preferably lower than the pressure at which the ion mobilityspectrometer or separator 3 is maintained. This preferably allows thefirst ion trap or ion guide 2 to be used more effectively to fragmentions by Collision Induced Decomposition than if the first ion trap orion guide 2 were maintained at the same pressure as that of the ionmobility spectrometer or separator 3. Accordingly, ions may be inducedto fragment in either the first ion trap or ion guide 2 and/or thesecond ion trap or ion guide 4.

FIG. 7 illustrates a mode of operation wherein ions are preferablyfragmented in the first ion trap or ion guide 2 in addition to beingfragmented in the second ion trap or ion guide 4. According to thisembodiment parent or precursor ions are preferably released from thefirst ion trap or ion guide 2 and preferably pass into the ion mobilityspectrometer or separator 3 as shown in step (a). The parent andprecursor ions are then preferably separated according to their ionmobility as the parent or precursor ions pass downstream through the ionmobility spectrometer or separator 3 as shown in step (b). The parent orprecursor ions exiting the ion mobility spectrometer or separator 3 arethen preferably accelerated out of the ion mobility spectrometer orseparator into the second ion trap or ion guide 4. This preferablycauses the parent or precursor ions to fragment into first generationfragment ions upon entering the second ion trap or ion guide 4. Separategroups of first generation fragment ions are preferably collected andkept isolated in separate real axial potential wells which arepreferably formed within the second ion trap or ion guide 4. The variousgroups of first generation fragment ions are preferably kept isolatedfrom one another and the DC voltages or potentials which are preferablyapplied to the electrodes of the second ion trap or ion guide 4 arepreferably held stationary so that the axial potential wells within thesecond ion trap or ion guide 4 are no longer translated downstreamtowards the mass analyser 5. One or more groups of first generationfragment ions trapped within the real axial potential wells formed orcreated within the second ion trap or ion guide 4 may then be discardedas shown in step (d). A first group of first generation fragment,daughter, product or adduct ions is then preferably released back intothe ion mobility spectrometer or separator 3 as shown in step (e).

The first group of first generation fragment, daughter, product oradduct ions is then preferably separated according to their ion mobilityas the first generation fragment, daughter, product or adduct ions passupstream back through the ion mobility spectrometer or separator 3. Thefirst generation fragment, daughter, product or adduct ions are thenpreferably accelerated out from the ion mobility spectrometer orseparator 3 and into the first ion trap or ion guide 2. This preferablycauses the first generation fragment, daughter, product or adduct ionsto be further fragmented into second generation fragment, daughter,product or adduct ions. The second generation fragment, daughter,product or adduct ions are preferably collected and stored in separatereal axial potential wells formed within the first ion trap or ion guide2. The second generation fragment or daughter ions resulting from thefragmentation of each first generation fragment or daughter ions arepreferably trapped or isolated in separate real axial potential wellscreated within the first ion trap or ion guide 2.

A first group of second generation fragment, daughter, product or adductions is then preferably released back into the ion mobility spectrometeror separator 3 as shown in step (h). The second generation fragment,daughter, product or adduct ions are then preferably separated accordingto their ion mobility as they pass downstream through the ion mobilityspectrometer or separator 3 and are preferably received by the secondion trap or ion guide 4. The separated second generation fragment,daughter, product or adduct ions are then preferably escorted ortranslated through the second ion trap or ion guide 4 to the massanalyser 5 for subsequent mass analysis. Second and further packets ofsecond generation fragment, daughter, product or adduct ions may then bereleased into the ion mobility spectrometer or separator 3 and may beseparated according to their ion mobility.

It is clear that a mass spectrometer as illustrated, for example, inFIG. 6 wherein ions may pass through the ion mobility spectrometer orseparator 3 in different directions either with or without beingseparated according to their ion mobility permits a large number ofdifferent permutations and combinations of sequences of operations to becarried out. Furthermore, ions may be induced to fragment upon exitingthe ion mobility spectrometer or separator 3 at either the downstreamand/or the upstream end of the ion mobility spectrometer or separator 3.As a result ions may be fragmented to a subsequent generation offragment, daughter, product or adduct ions upon each passage of ionsthrough the ion mobility spectrometer or separator 3 as and whenrequired.

According to other less preferred embodiments ions may be fragmented bymeans other than by high energy collisions with gas molecules. Forexample, fragmentation techniques such as photo-dissociation, ElectronCapture Dissociation (ECD), Electron Transfer Dissociation (ETD) andSurface Induced Decomposition (SID) may be used in order to fragmentions.

According to another embodiment when ions leave the ion mobilityspectrometer or separator 3 the ions may instead be only partiallyenergised by collisions with gas molecules such that instead of causingions to be fragmented, the internal energy of the ions is preferablyraised causing the ions to unfold or partially unfold withoutfragmenting. The ions may therefore be caused to change shape, structureor conformation. This may be achieved by raising the kinetic energy ofthe ions leaving the ion mobility spectrometer or separator 3 to a levelthat promotes an increase in internal energy without inducingfragmentation. The resulting change in cross section and hence ionmobility may then be measured or determined by passing the ions throughthe ion mobility spectrometer or separator 3 and determining any changein the transit time of the ions through the ion mobility spectrometer orseparator 3.

According to another less preferred embodiment a Field Asymmetric IonMobility Spectrometer or FAIMS device may be provided instead of or inaddition to an ion mobility spectrometer or separator 3. The FieldAsymmetric Ion Mobility Spectrometer device is preferably arranged toseparate ions according to their rate of change of ion mobility withelectric field strength.

Although the present invention has been described with reference topreferred embodiments, it will be understood by those skilled in the artthat various changes in form and detail may be made without departingfrom the scope of the present invention as set forth in the accompanyingclaims.

1. A mass spectrometer comprising: a first ion trap or ion guidecomprising a plurality of electrodes; a device for separating ionsaccording to their ion mobility or rate of change of ion mobility withelectric field strength, said device being arranged downstream of saidfirst ion trap or ion guide; first transient DC voltage means arrangedand adapted to apply one or more transient DC voltages or one or moretransient DC voltage waveforms to electrodes forming said device; and asecond ion trap or ion guide comprising a plurality of electrodesarranged downstream of said device, wherein said second ion trap or ionguide is arranged and adapted to receive a beam or group of ions and topartition said beam or group of ions such that a plurality of separatepackets of ions are confined in said second ion trap or ion guide at anyparticular time, wherein each packet of ions is separately confined in aseparate axial potential well formed within said second ion trap or ionguide.
 2. A mass spectrometer as claimed in claim 1, wherein said firstion trap or ion guide is arranged and adapted in a mode of operation toreceive ions which emerge from said device and to pass or transmit atleast some of said ions, or at least some fragment, daughter, product oradduct ions derived from said ions, from said first ion trap or ionguide to said device.
 3. A mass spectrometer as claimed in claim 1,wherein said first ion trap or ion guide is arranged and adapted toreceive a beam or group of ions and to convert or partition said beam orgroup of ions such that a plurality or at least 1, 2, 3, 4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 separate packets of ionsare confined or isolated in said first ion trap or ion guide at anyparticular time, and wherein each packet of ions is separately confinedor isolated in a separate axial potential well formed within said firstion trap or ion guide.
 4. A mass spectrometer as claimed in claim 1,further comprising: (i) first acceleration means arranged and adapted toaccelerate ions into said first ion trap or ion guide wherein in a modeof operation at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of said ions arecaused to fragment or react upon entering said first ion trap or ionguide; or (ii) second acceleration means arranged and adapted toaccelerate ions into said second ion trap or ion guide wherein in a modeof operation at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of said ions arecaused to fragment or react upon entering said second ion trap or ionguide.
 5. A mass spectrometer as claimed in claim 1, further comprisinga control system arranged and adapted to switch or repeatedly switch thepotential difference through which ions pass prior to entering saidfirst ion trap or ion guide or said second ion trap or ion guide betweena relatively high fragmentation or reaction mode of operation whereinions are substantially fragmented or reacted upon entering said secondion trap or ion guide and a relatively low fragmentation or reactionmode of operation wherein substantially fewer ions are fragmented orreacted or wherein substantially no ions are fragmented or reacted uponentering said second ion trap or ion guide.
 6. A mass spectrometer asclaimed in claim 1, further comprising (a) an ion source selected fromthe group consisting of: (i) an Electrospray ionisation (“ESI”) ionsource; (ii) an Atmospheric Pressure Photo Ionisation (“APPI”) ionsource; (iii) an Atmospheric Pressure Chemical Ionisation (“APCI”) ionsource; (iv) a Matrix Assisted Laser Desorption Ionisation (“MALDI”) ionsource; (v) a Laser Desorption Ionisation (“LDI”) ion source; (vi) anAtmospheric Pressure Ionisation (“API”) ion source; (vii) a DesorptionIonisation On Silicon (“DIOS”) ion source; (viii) an Electron Impact(“EI”) ion source; (ix) a Chemical Ionisation (“CI”) ion source; (x) aField Ionisation (“FI”) ion source; (xi) a Field Desorption (“FD”) ionsource; (xii) an Inductively Coupled Plasma (“ICP”) ion source; (xiii) aFast Atom Bombardment (“FAB”) ion source; (xiv) a Liquid Secondary IonMass Spectrometry (“LSIMS”) ion source; (xv) a Desorption ElectrosprayIonisation (“DESI”) ion source; (xvi) a Nickel-63 radioactive ionsource; (xvii) an Atmospheric Pressure Matrix Assisted Laser DesorptionIonisation (“AP-MALDI”) ion source; and (xviii) a Thermospray ionsource; or (b) a collision, fragmentation or reaction device selectedfrom the group consisting of: (i) a collision, fragmentation or reactiondevice arranged and adapted to fragment ions by Collision InducedDissociation (“CID”); (ii) a Surface Induced Dissociation (“SID”)fragmentation device; (iii) an Electron Transfer Dissociationfragmentation device; (iv) an Electron Capture Dissociationfragmentation device; (v) an Electron Collision or Impact Dissociationfragmentation device; (vi) a Photo Induced Dissociation (“PID”)fragmentation device; (vii) a Laser Induced Dissociation fragmentationdevice; (viii) an infrared radiation induced dissociation device; (ix)an ultraviolet radiation induced dissociation device; (x) anozzle-skimmer interface fragmentation device; (xi) an in-sourcefragmentation device; (xii) an ion-source Collision Induced Dissociationfragmentation device; (xiii) a thermal or temperature sourcefragmentation device; (xiv) an electric field induced fragmentationdevice; (xv) a magnetic field induced fragmentation device; (xvi) anenzyme digestion or enzyme degradation fragmentation device; (xvii) anion-ion reaction fragmentation device; (xviii) an ion-molecule reactionfragmentation device; (xix) an ion-atom reaction fragmentation device;(xx) an ion-metastable ion reaction fragmentation device; (xxi) anion-metastable molecule reaction fragmentation device; (xxii) anion-metastable atom reaction fragmentation device; (xxiii) an ion-ionreaction device for reacting ions to form adduct or product ions; (xxiv)an ion-molecule reaction device for reacting ions to form adduct orproduct ions; (xxv) an ion-atom reaction device for reacting ions toform adduct or product ions; (xxvi) an ion-metastable ion reactiondevice for reacting ions to form adduct or product ions; (xxvii) anion-metastable molecule reaction device for reacting ions to form adductor product ions; and (xxviii) an ion-metastable atom reaction device forreacting ions to form adduct or product ions; or (c) mass analyser isselected from the group consisting of: (i) a quadrupole mass analyser;(ii) a 2D or linear quadrupole mass analyser; (iii) a Paul or 3Dquadrupole mass analyser; (iv) a Penning trap mass analyser; (v) an iontrap mass analyser; (vi) a magnetic sector mass analyser; (vii) IonCyclotron Resonance (“ICR”) mass analyser; (viii) a Fourier TransformIon Cyclotron Resonance (“FTICR”) mass analyser; (ix) an electrostaticor orbitrap mass analyser; (x) a Fourier Transform electrostatic ororbitrap mass analyser; (xi) a Fourier Transform mass analyser; (xii) aTime of Flight mass analyser; (xiii) an orthogonal acceleration Time ofFlight mass analyser; (xiv) an axial acceleration Time of Flight massanalyser; and (xv) a quadrupole rod set mass filter or mass analyser. 7.A mass spectrometer as claimed in claim 1, further comprising a massfilter or mass analyser, wherein said mass filter or mass analyser isselected from the group consisting of: (i) a quadrupole rod set massfilter or mass analyser; (ii) a Time of Flight mass filter or massanalyser; (iii) a Wein filter; and (iv) a magnetic sector mass filter ormass analyser; and wherein in a mode of operation: (i) said mass filteror mass analyser is operated in a substantially non-resolving or ionguiding mode of operation; or (ii) said mass filter or mass analyser isscanned or a mass to charge ratio transmission window of said massfilter or mass analyser is varied with time.
 8. A mass spectrometer asclaimed in claim 1, wherein in a mode of operation a first mass filteror mass analyser or a second mass filter or mass analyser is scanned ora mass to charge ratio transmission window of said first mass filter ormass analyser or said second mass filter or mass analyser is varied withtime in synchronism with the operation of said device or the ionmobility or rate of change of ion mobility with electric field strengthof ions emerging from or being transmitted to said device.
 9. A massspectrometer as claimed in claim 1, further comprising an ion gate ordeflection system arranged upstream or downstream of said device.
 10. Amass spectrometer as claimed in claim 1, wherein said device comprises:(i) a drift tube comprising one or more electrodes and means formaintaining an axial DC voltage gradient or a substantially constant orlinear axial DC voltage gradient along at least 5%, 10%, 15%, 20%, 25%,30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or100% of the axial length of said drift tube; (ii) a multipole rod set ora segmented multipole rod set comprising a quadrupole rod set, ahexapole rod set, an octapole rod set or a rod set comprising more thaneight rods; (iii) an ion tunnel or ion funnel comprising a plurality ofelectrodes or at least 2, 5, 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100electrodes having apertures through which ions are transmitted in use,wherein at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%,60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% of said electrodes haveapertures which are of substantially the same size or area or which haveapertures which become progressively larger or smaller in size or inarea; (iv) a stack or array of planar, plate or mesh electrodes, whereinsaid stack or array of planar, plate or mesh electrodes comprises aplurality or at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15,16, 17, 18, 19 or 20 planar, plate or mesh electrodes wherein at least5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%,75%, 80%, 85%, 90%, 95% or 100% of said planar, plate or mesh electrodesare arranged generally in the plane in which ions travel in use; and (v)a plurality of groups of electrodes arranged axially along the length ofthe ion trap or ion guide, wherein each group of electrodes comprises:(a) a first and a second electrode and means for applying a DC voltageto said first and second electrodes in order to confine ions in a firstradial direction within said device; and (b) a third and a fourthelectrode and means for applying an RF voltage to said third and fourthelectrodes in order to confine ions in a second radial direction withinsaid device.
 11. A mass spectrometer as claimed in claim 1, wherein saiddevice further comprises an RF voltage means arranged and adapted toapply an RF voltage to at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%,45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 100% to aplurality of electrodes forming said device in order to confine ionsradially within said device.
 12. A mass spectrometer as claimed in claim1, wherein said first transient DC voltage means is arranged and adaptedto urge at least some ions upstream or downstream along at least 5%,10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%,80%, 85%, 90%, 95% or 100% of the axial length of said device.
 13. Amass spectrometer as claimed in claim 1, wherein said second ion trap orion guide is arranged in a mode of operation to pass or transmit ionsfrom said second ion trap or ion guide to said first ion trap or ionguide.
 14. A mass spectrometer as claimed in claim 13, wherein saidsecond ion trap or ion guide is arranged in a mode of operation to passor transmit ions from said second ion trap or ion guide to first iontrap or ion guide multiple times before transporting said ions to a massanalyser for subsequent mass analysis.
 15. A method of mass spectrometrycomprising: providing a first ion trap or ion guide; separating ionsaccording to their ion mobility or rate of change of ion mobility withelectric field strength in a device, said device being arrangeddownstream of said first ion trap or ion guide; applying one or moretransient DC voltages or one or more transient DC voltage waveforms toelectrodes forming said device; providing a second ion trap or ion guidearranged downstream of said device; receiving a beam or group of ions insaid second ion trap or ion guide and partitioning said beam or group ofions such that a plurality of separate packets of ions are confined insaid second ion trap or ion guide at any particular time, wherein eachpacket of ions is separately confined in a separate axial potential wellformed within said second ion trap or ion guide.
 16. A method of massspectrometry comprising: providing a first ion trap or ion guide;providing a device for separating ions according to their ion mobilityor rate of change of ion mobility with electric field strength, saiddevice being arranged downstream of said first ion trap or ion guide;providing a second ion trap or ion guide arranged downstream of saidfirst ion trap or guide; and passing ions from said first ion trap orion guide to said device and onwards to said second ion trap or ionguide; and then passing at least some of said ions or at least somefragment, daughter, product or adduct ions derived from said ions fromsaid second ion trap or ion guide onwards to said first ion trap or ionguide.
 17. A method as claimed in claim 16, comprising forming aplurality of potential wells within said second ion trap or ion guideand partitioning multiple ions present in said second ion trap or ionguide at the same time into a plurality of separate packets of ionswherein each packet of ions is separately confined in a separate of saidaxial potential wells.
 18. A method as claimed in claim 16, comprisingrepeating the steps of passing ions from said first ion trap or ionguide to said device and onwards to said second ion trap or ion guideand then passing at least some of said ions or at least some fragment,daughter, product or adduct ions derived from said ions from said secondion trap or ion guide to said first ion trap or ion guide multipletimes.
 19. A method as claimed in claim 18, comprising varying thenumber of passes of ions through said device.
 20. A method as claimed inclaim 18, comprising, at the end of each cycle of operation,transporting ions from said second ion trap or ion guide to a massanalyser for subsequent mass analysis.
 21. A mass spectrometercomprising: a first ion trap or ion guide; a device for separating ionsaccording to their ion mobility or rate of change of ion mobility withelectric field strength, said device being arranged downstream of saidfirst ion trap or ion guide; and a second ion trap or ion guide arrangeddownstream of said first ion trap or guide wherein said first ion trapor ion guide is arranged to pass or transmit ions to said device andonwards to said second ion trap or ion guide, and wherein said secondion trap or ion guide is arranged to pass at least some of said ions orat least some fragment, daughter, product or adduct ions derived fromsaid ions onwards to said first ion trap or ion guide.